Polymersomes and related encapsulating membranes

Abstract

The present invention provides biocompatible vesicles comprising semi-permeable, thin-walled encapsulating membranes which are formed in an aqueous solution, and which comprise one or more synthetic super-amphiphilic molecules. When at least one super-amphiphile molecule is a block copolymer, the resulting synthetic vesicle is termed a “polymersome.” The synthetic, reactive nature of the amphiphilic composition enables extensive, covalent cross-linking of the membrane, while maintaining semi-permeability. Cross-linking of the polymer building-block components provides mechanical control and long-term stability to the vesicle, thereby also providing a means of controlling the encapsulation or release of materials from the vesicle by modifying the composition of the membrane. Thus, the encapsulating membranes of the present invention are particularly suited for the reliable, durable and controlled transport, delivery and storage of materials.

Description

GOVERNMENT SUPPORT[0001]This work was supported in part by grants from the National Science Foundation, grant numbers DMR96-32598 and DMR 98-09364, and also by grants from the Whitaker Foundation and the National Institutes of Health, grant numbers R01-HL62352-01 and P01-HLI8208. The government may have certain rights in this invention.FIELD OF THE INVENTION[0002]The present invention relates to the preparation and use of vesicles and related encapsulating membranes made in aqueous solution from amphiphilic polymers and related molecules.BACKGROUND OF THE INVENTION[0003]Membranes that are stable in aqueous media are heavily relied upon for compartmentalization by biological cells. For instance, the outermost plasma membrane of a cell separates the inside of a cell from the outside and, like most cell membranes, it is a self-assembled, complex fluid of biological molecules, primarily lipids and proteins. Only a few molecules, such as water and small, uncharged organic molecules, sign...

AI Technical Summary

Benefits of technology

[0015]The present invention meets the need in the art by providing not only an illustrative set of stable super-amphiphilic vesicles in biocompatible, aqueous solutions, but it also provides vesicles which are entirely synthetic, creating an opportunity to tailor the dynamics, structure, Theological and even optical responses of the membrane based on its composition. The polymer vesicles of the present invention are called “polymersomes.” Analogous to “liposomes” made from phospholipids, the material properties of the polymersome vesicles can be readily measured using techniques that have been largely developed for phospholipid vesicles and biological cells. Furthermore, the ability to cross-link the polymer building blocks affords a novel opportunity to provide mechanical control and stability to the vesicle on the order of that which is provided by the protein skeleton at a cell's plasma membrane.

[0016]Polymersomes of the present invention possess membranes capable of self-repair, adaptability, portability, resilience, and are selectively permeable, thereby providing, for example, long-term, reliable and controllable vehicles for the delivery or storage of drugs or other compositions, such as oxygen, to the patient via the bloodstream, gastrointestinal tract, or other tissues, as replacement artificial tissue or soft biomaterial, as optical sensors, and as a structural basis for metal or alloy coatings to provide materials having unique electric or magnetic properties for use in high-dielectric or magnetic applications or as microcathodes.

[0020]Further provided in the present invention are reactive amphiphiles that can be covalently cross-linked together, over a many micron-squared surface, while maintaining semi-permeability of the membrane. Cross-linked polymersome are characterized as having the ability to withstand exposure to organic solvents, boiling water, dehydration and rehydration in an aqueous solution without visibly or significantly affecting the integrity of the membrane.

Problems solved by technology

Phospholipid vesicles are materially weak and environmentally sensitive.

However, a fully, covalently interconnected network of lipids requires complete cross-linking of the membrane of a vesicle, and the full extent of cross-linking achievable with cross-linkable lipids appears to be difficult to ascertain.

It is clear, however, that no fully cross-linked lipid vesicle larger than several hundred nanometers has been reported.

However, bilayer filaments and superhelical rods existed, without explanation, under the same solution conditions, thus making the stability of the collapsed vesicles, relative to the other microstructures, highly uncertain for the studied dipeptide-base copolymer.

Furthermore, no demonstration of semi-permeability was reported, and reasons for apparent vesicle collapse were not given, further raising questions of vesicle stability.

However, there appears in the prior art only one example of a wholly synthetic super-amphiphile that has the unpredicted capacity to self-assemble in aqueous solution, albeit only under moderately acidic pH conditions, into a vesicle-like microstructure, and that is the reported work of Cornelissen et al., 1998, although even those structures were of questionable state and stability.

In the absence of cross-linking, microstructures of amphiphiles and super-amphiphiles are generally unstable to treatments that could otherwise prove very useful for a range of applications that might benefit from, for example, sterilization, or long-term dry storage.

Images